E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Unresectable/metastatic breast cancer with HER2 positive expression |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•Objective response rate (ORR) per imaging assessment - Percentage of participants with objective response is assessed every six weeks from Cycle 1 Day 1 through disease progression, by independent central imaging facility review based on RECIST version 1.1 |
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E.2.2 | Secondary objectives of the trial |
●Duration of response ●Best percent change in the sum of diameters of measurable tumors ●Disease control rate (DCR) ●Clinical benefit rate (CBR) ●Progression-free survival ●Overall survival (OS) ●ORR assessed by the investigator based on RECIST version 1.1
The following apply to categories; DS-8201a, total anti-HER2 antibody and MAAA-1181a: ●Maximum plasma/serum concentration (Cmax) ●Time to Cmax (Tmax) ●Area under the concentration-time curve (AUC) from dosing until the last quantifiable concentration (AUClast) ●AUC from the time of dosing until day 21 (AUC0-21d) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Men or women the age of majority in their country •Has pathologically documented breast cancer that: 1.is unresectable or metastatic 2.has HER2 positive expression confirmed per protocol •Has an adequate tumor sample •Has at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 •Has protocol-defined adequate cardiac, renal and hepatic function •Agrees to follow protocol-defined method(s) of contraception |
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E.4 | Principal exclusion criteria |
•Has a medical history of myocardial infarction, symptomatic congestive heart failure (CHF) (NYHA classes II-IV), unstable angina or serious cardiac arrhythmia •Has a QTc prolongation to > 450 millisecond (ms) in males and > 470 ms in females •Has a medical history of clinically significant lung disease •Is suspected to have certain other protocol-defined diseases based on imaging at screening period •Has history of any disease, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise: 1.safety or well-being of the participant or offspring 2.safety of study staff 3.analysis of results |
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E.5 End points |
E.5.1 | Primary end point(s) |
ORR assessed by independent central imaging facility review based on RECIST version 1.1.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints include: a) Duration of response, best percent change in the sum of diameters of measurable tumors, DCR, clinical benefit ratio (CBR), PFS, OS, and ORR assessed by the investigator based on RECIST version 1.1. b) Maximum plasma/serum concentration (Cmax), Time to Cmax (Tmax), Area under the concentration-time curve (AUC) from dosing until the last quantifiable concentration (AUClast), AUC from the time of dosing until day 21 (AUC0-21d) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For endpoints: a) 22 months b) 21 days |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Japan |
Korea, Republic of |
United States |
Belgium |
France |
Italy |
Spain |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 22 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 22 |